The overall objective of this proposal is to investigate an immunoregulatory system involving T cells bearing histamine receptors. It has been well established by this and other laboratories that stimulation of histamine receptor bearing T cells modulates both humoral and cellular immune reactions in vitro. The specific aims of this proposal will include the following lines of investigation: 1. Evaluation of the role of cyclo-oxygenase metabolites such as PGE2, PGD2, PGF2Alpha, PFG1Alpha, and TxB2, as well as 5-lipoxygenase products LTB4, LTC4, LTD4, LTE4, 5-HETE and 12-HETE on the lectin-induced lymphocyte proliferative response of normal subjects. Similar experiments will be carried out in atopic subjects and their responses compared. 2. Develop a profile of arachidonic acid metabolites generated by histamine suppressor factor (HSF)-stimulated monocytes obtained from non-atopic subjects. These experiments will then be carried out using monocytes from atopic patients and qualitative and/or quantitative differences in their response documented, compared to non-atopic subjects. These studies may reveal differences in the utilization of arachidonic acid by atopic cells or perhaps a defect in its metabolism. 3. Differences in arachidonic acid metabolism by atopic monocytes in response to HSF will be pursued in terms of a biochemical analyses of early events in "activation" of monocytes by HSF. Specifically phospholipid membrane turnover studies, Ca++ flux, cAMP levels, adenylate cyclase activity and cAMP-dependent protein kinase activity will be measured in HSF-stimulated normal and atopic monocytes. 4. Study the effects of HSF on the production of T cell growth factor and expression of IL-2 receptors of proliferating T cells. 5. Purification of HSF by means of hydrophobic chromotography, gel filtration and isoelectric focussing. 6. Generation of monoclonal antibodies against human HSF using hybridoma techniques. Material generated by histamine-stimulated human lymphocytes and/or a cell line product and purified by the above methodologies will be used to immunize mice for the production of monoclonal antibodies.